Synthesis and formylation of 5-piperidino-2,2´-bithiophene

Abstract

The aim of this work is the synthesis of a 5-N,N-dialkylamino-2,2´-bithiophene as well as its 4- and 5´-formyl derivatives through several synthetic transformations, namely: i) thionation of carbonyl groups of a tertiary gama-ketoamide derived from thiophene using Lawesson´s reagent followed by cyclization of the corresponding thioxoamide through intramolecular nucleophilic attack yielding the 5-N,N-dialkylamino-2-2´-bithiophene derivative; formylation of the bithiophene derivative using two different synthetic methodologies: ii) Vilsmeier-Haack reaction or iii) lithiation followed by electrophilic aromatic substitution. The formylation of 5- piperidino -2 , 2'- bithiophene via two different methods of synthesis selectively yields two different products (4- or 5´-formyl derivatives), leading to a discussion concerning the selectivity of each reaction having in mind the reagents used in each method as well as the mechanism of these transformations. Several experimental techniques will be considered such as heating at reflux in under anhydrous conditions with an inert atmosphere, liquid-liquid extraction, gravity filtration, thin layer chromatography (TLC), column chromatography using silica gel and melting point analysis. The determination of the structure of all compounds synthesized will be also performed through 1H NMR, 13C NMR, IR and UV spectroscopic techniques. The duration of the experiment will be 6 sessions: session 1: preparation of 5- piperidino -2,2'- bithiophene; session 2: purification of 5- piperidino -2,2'- bithiophene using column chromatography with silica gel, session 3: preparation of 4-formyl-5-piperidino-2,2´-bithiophene, session 4: purification of 4-formyl-5-piperidino-2,2´-bithiophene using column chromatography with silica gel, session 5: preparation of 5´-formyl-5-piperino-2,2'- bithiophene, session 6: purification of 5´-formyl-5-piperino-2 ,2'- bithiophene using column chromatography with silica gel. The difficulty level of this experiment is high and the level of study is intermediate.